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Presents a study using image restoration, to investigate three-dimensional super-resolution with a 4Pi-confocal microscope. Information on the concept of 4Pi-confocal microscopy; Details on resolution improvement through image restoration; Application of restoration procedures to standard confocal imaging; Conclusion reached on the study.

Background: Investigations of the effect of beverages containing carbohydrates, only, on the sodium and fluid balance during intermittent exercise of high intensity are rare. Therefore, we compared the effects of water and carbohydrate supplementation on plasma, blood volume, and electrolyte shifts during intermittent exercise.Methods: Ten male subjects performed an intermittent exercise test twice. In one trial, tap water (4 ml/kg/15 min) was consumed (Plac trial). In the other trial, the same amount of water supplemented with maltodextrin to achieve a 9.1 % carbohydrate solution (CHO trial) was ingested. Training schedule: warm-up at 50 % for 15 min. Afterwards, power changed between 100 % of the maximum power from a previous incremental test minus 10 and 10 W for each 30 s. Venous blood was sampled to measure electrolytes, osmolality, [protein], hct, [Lactate], [glucose], [Hb] and catecholamines. Hydration status was evaluated by BIA before and after exercise.Results: After beverage ingestion [glucose] was significantly higher in CHO until the end of the trial. Starting with similar resting values, osmolality increased significantly more during CHO (p = 0.002). PV decreased by 5 % under both conditions, but recovered partly during exercise under Plac (p = 0.002). [Na+] and [Cl(-)] decreased with Plac during exercise (both p < 0.001) but remained constant during exercise with CHO.Conclusions: Sole carbohydrate supplementation seems to stabilise plasma [Na+]. This cannot be explained simply by a cotransport of glucose and [Na+], because that should lead to a recovery of the blood and plasma volume under CHO. In contrast, this was found during exercise with Plac. [ABSTRACT FROM AUTHOR]

Abstract: Peroxisomes are remarkably dynamic, multifunctional organelles, which react to physiological changes in their cellular environment and adopt their morphology, number, enzyme content and metabolic functions accordingly. At the organelle level, the key molecular machinery controlling peroxisomal membrane elongation and remodeling as well as membrane fission is becoming increasingly established and defined. Key players in peroxisome division are conserved in animals, plants and fungi, and key fission components are shared with mitochondria. However, the physiological stimuli and corresponding signal transduction pathways regulating and modulating peroxisome maintenance and proliferation are, despite a few exceptions, largely unexplored. There is emerging evidence that peroxisomal dynamics and proper regulation of peroxisome number and morphology are crucial for the physiology of the cell, as well as for the pathology of the organism. Here, we discuss several key aspects of peroxisomal fission and proliferation and highlight their association with certain diseases. We address signaling and transcriptional events resulting in peroxisome proliferation, and focus on novel findings concerning the key division components and their interplay. Finally, we present an updated model of peroxisomal growth and division. This article is part of a Special Issue entitled: Metabolic Functions and Biogenesis of Peroxisomes in Health and Disease. [Copyright &y& Elsevier]

Abstract: At the Max-Plank-Institute for plasma physics (IPP) in Greifswald, the stellerator Wendelstein 7-X (W7-X) is under construction. The toroidal plasma with a major diameter of 11m is enclosed by a plasma vessel, whose geometrical shape closely follows the shape of the plasma-beam. The plasma vessel supporting system is divided into two separate subsystems, the horizontal support system and the vertical support system (VSS). The assignment of the horizontal support system is to centre and to adjust the plasma vessel during radial thermal expansion in the horizontal direction. The vertical support system is designed to resist the plasma vessel dead weight and other vertical loads coming from attached structures and to allow a vertical adjustment. This paper describes the design of the VSS and the testing conducted at the University of Rostock to validate the design. [Copyright &y& Elsevier]

: ObjectivesTo examine the usefulness of pretreatment testicular sperm extraction because some patients have tumor-induced azoospermia. In view of the high cure rates for testicular germ cell tumors and malignant lymphomas, increasing clinical importance is attached to protecting fertility. High-dose cytostatic therapy may be expected to cause long-term infertility. Thus, the standard procedure for fertility protection is cryopreservation of ejaculated spermatozoa before therapy.: MethodsContralateral testicular biopsies were taken from 14 azoospermic patients with malignant testicular germ cell tumors. In addition, 17 patients with malignant lymphomas underwent unilateral (n = 6) or bilateral (n = 11) testicular biopsy. The tissue specimens were cryopreserved, and the histologic workup was performed at the same time.: ResultsOf the 14 patients with malignant testicular germ cell tumors, 6 had spermatozoa in their testicular biopsies. Sertoli cell-only syndrome was found in 5 patients, and 3 had maturation arrest without detection of spermatozoa. Successful sperm recovery was possible in 8 of the 17 patients with malignant lymphoma, 4 had Sertoli cell-only syndrome, and 5 had maturation arrest. None of the patients had evidence of secondary wound healing or treatment delay because of the testicular biopsy.: ConclusionsOur results show that testicular sperm extraction is a useful technique for obtaining spermatozoa before cytotoxic therapy in azoospermic cancer patients. This procedure should be considered as an option for fertility preservation in azoospermic cancer patients, because high cumulative cytostatic doses can cause irreversible fertility alterations. [Copyright &y& Elsevier]

The aim of the study was to evaluate the quantitative detection of human telomerase reverse transcriptase (hTERT) mRNA and telomerase activity as new molecular diagnostic parameters for a subclassification of spermatogenesis disorders. Telomerase activity was detected by a quantitative telomerase PCR ELISA, and hTERT mRNA expression was quantified by fluorescence real-time RT–PCR in a LightCycler® in cryopreserved testicular tissue specimens. This was paralleled by a histological workup. The discriminant analysis showed that detection of normalized hTERT expression was able to correctly classify 89.0% of the investigated tissue specimens into the subgroups of full spermatogenesis, maturation arrest or Sertoli-cell-only syndrome. In contrast, discriminant analysis revealed an only 58% accuracy of telomerase activity for the investigated tissue specimens. This study shows that the quantification of hTERT expression in testicular tissue by real-time fluorescence RT–PCR is well suited for correctly classifying spermatogenesis disorders and proved to be markedly superior to the determination of telomerase activity. [ABSTRACT FROM AUTHOR]

We determine the resolution of high-performance confocal microscopes by measuring the three-dimensional point–spread function (3D-PSF) of an optimized confocal setup. The 3D-PSF is standardized by recording the scattered light of pointlike objects. For a wavelength of 543 nm and a specified numerical aperture of 1.4 (oil), we find an axial and lateral focal full width at half-maximum (FWHM) of 460±20 and 145±10 nm, respectively. A high signal-to-noise ratio is obtained by using recording times comparable to those of near-field scanning optical microscopy. We further reduce the effective PSF extent by means of a three-dimensional deconvolution technique exploiting the information gained from the measurement of the focus. We show that it is possible to obtain an axial and lateral FWHM of the far-field effective PSF after deconvolution of 80 and 40 nm, respectively. © 1996 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Background:Resistance to cisplatin-based chemotherapy is associated with poor prognosis in testicular germ cell cancer, emphasising the need for new therapeutic approaches. In this respect, the therapeutic concept of anti-angiogenesis is of particular interest. In a previous study, we presented two novel anti-angiogenic compounds, HP-2 and HP-14, blocking the tyrosine kinase activity of angiogenic growth factor receptors, such as vascular endothelial growth factor receptor-2 (VEGFR-2), and related signalling pathways in testicular cancer. In this study, we investigated the efficacy of these new compounds in platinum-resistant testicular germ cell tumours (TGCTs), in vitro and in vivo.Methods and results:Drug-induced changes in cell proliferation of the cisplatin-sensitive TGCT cell line 2102EP and its cisplatin-resistant counterpart 2102EP-R, both expressing the VEGFR-2, were evaluated by crystal violet staining. Both compounds inhibited the growth of cisplatin-resistant TGCT cells in a dose-dependent manner. In combination experiments with cisplatin, HP-14 revealed additive growth-inhibitory effects in TGCT cells, irrespective of the level of cisplatin resistance. Anti-angiogenic effects of HP compounds were confirmed by tube formation assays with freshly isolated human umbilical vein endothelial cells. Using TGCT cells inoculated onto the chorioallantoic membrane of fertilised chicken eggs (chicken chorioallantoic membrane assay), the anti-angiogenic and anti-proliferative potency of the novel compounds was also demonstrated in vivo. Gene expression profiling revealed changes in the expression pattern of genes related to DNA damage detection and repair, as well as in chaperone function after treatment with both cisplatin and HP-14, alone or in combination. This suggests that HP-14 can revert the lost effectiveness of cisplatin in the resistant cells by altering the expression of critical genes.Conclusion:The novel compound HP-14 effectively inhibits the growth of cisplatin-resistant TGCT cells and suppresses tumour angiogenesis. Thus, HP-14 may be an interesting new agent that should be further explored for TGCT treatment, especially in TGCTs that are resistant to cisplatin. [ABSTRACT FROM AUTHOR]

Abstract: Peroxisomes represent so-called “multipurpose organelles” as they contribute to various anabolic as well as catabolic pathways. Thus, with respect to the physiological specialization of an individual organ or animal species, peroxisomes exhibit a functional diversity, which is documented by significant variations in their proteome. These differences are usually regarded as an adaptational response to the nutritional and environmental life conditions of a specific organism. Thus, human peroxisomes can be regarded as an in part physiologically unique organellar entity fulfilling metabolic functions that differ from our animal model systems. In line with this, a profound understanding on how peroxisomes acquired functional heterogeneity in terms of an evolutionary and mechanistic background is required. This review summarizes our current knowledge on the heterogeneity of peroxisomal physiology, providing insights into the genetic and cell biological mechanisms, which lead to the differential localization or expression of peroxisomal proteins and further gives an overview on peroxisomal biochemical pathways, which are specialized in different animal species and organs. Moreover, it addresses the impact of proteome studies on our understanding of differential peroxisome function describing the utility of mass spectrometry and computer-assisted algorithms to identify peroxisomal target sequences for the detection of new organ- or species-specific peroxisomal proteins. [Copyright &y& Elsevier]

Background: Testicular germ cell tumour (TGCT) is the most common cause of death from solid tumours in young men and especially for platinum-refractory patients novel treatment approaches are urgently needed. Using an in silico screening approach for the detection of novel cancer drugs with inhibitory effects on the tyrosine kinase activity of growth factors (e.g., VEGFR, PDGFR), we identified two compounds (HP-2 and HP-14) with antiangiogenic and antiproliferative potency, which were evaluated in endothelial cell models and TGCT cells.Results: HP-2 and HP-14 effectively inhibited the growth of VEGFR-2-expressing TGCT cell lines (Tera-1, Tera-2 and 2102EP) and endothelial cell models, while they failed to supress the growth of VEGFR-2-lacking tumour cells. cDNA-microarrays revealed an inhibition of the expression of several growth factor receptors and related signal transduction molecules. Vascular endothelial growth factor (VEGF)-induced cell migration was also potently inhibited. Cell cycle-regulating proteins such as p21 and p27 were upregulated, leading to an S-phase arrest. Additional in vivo evaluations confirmed the antiangiogenic potency and good tolerability of the novel substances.Conclusion: Our data show that the identified novel compounds inhibit the growth of TGCT cells and decrease angiogenic microvessel formation. The mode of action involves cell cycle arresting effects and changes in the expression pattern of several angiogenic genes. The novel compounds may qualify as new candidates for targeted treatment of TGCT and merit further evaluation. [ABSTRACT FROM AUTHOR]

Abstract: At the Max-Planck-Institut für Plasmaphysik (IPP) the new stellarator fusion experiment WENDELSTEIN 7-X (W7-X) is under construction. Its ultimate goal is to verify that stellarator magnetic confinement concept is a viable option for a demonstration fusion power-plant. Its toroidal plasma (major diameter of 11m) is enclosed by a cryostat. The Outer Vessel (OV), ports and the vacuum vessel (VV) accumulate the cryostat together. The main functions of the VV supports (VVS) are to withstand and transfer all vertical forces from the VV to the machine base and to allow horizontal movements simultaneously. Therefore, pendulum support system was introduced. The paper will describe their design and the destinations and results of a test campaigns (scale 1:1) at the University of Rostock. [Copyright &y& Elsevier]

Species pairs whose distributions are tied to environmental conditions provide intriguing candidates for the study of ecological speciation. Here, we examine the role that adaptation to salinity has played in the divergence between two closely related species, Lucania goodei and Lucania parva, whose distributions reflect salinity ( L. goodei– fresh water, L. parva– euryhaline). We first tested whether these two species display local adaptation and, subsequently, tested for ecological, genic and behavioural isolation by performing crosses within and between L. goodei and L. parva and raising offspring under various salinities. We found strong evidence for differential adaptation to salinity and also for behavioural isolation where animals preferentially mated with conspecifics over heterospecifics. However, we found no evidence for F1 hybrid inviability. We discuss the general lack of evidence for genic isolation in teleost fish and whether this is a real phenomenon or simply a reflection of experimental design. [ABSTRACT FROM AUTHOR]

Objectives To clarify in vivo , using isolated small intestinal loops perfused with radioactive 14 C-oxalate, whether intestinal hyperabsorption or reduced secretion is important in magnesium deficiency (MgD), as this is a potential cause of calcium oxalate urolithiasis. Materials and methods Twenty-four Sprague-Dawley rats were either fed a standard diet (control, 12 rats) or a magnesium-deficient diet (MgD, 12 rats) for 19 weeks. One hour before the animals were killed, a defined length of a small intestinal loop was isolated and filled with 5 mL of 0.9% NaCl and a defined amount of intravenous 14 C-oxalate applied. Using this method it was possible to determine the secretion of unlabelled oxalate into the intestinal lumen, from the specific activity in plasma. Results Plasma oxalate levels doubled under MgD; urinary calcium and phosphorus also increased significantly, while urine oxalate tended to decrease. The secretion of oxalate into the intestinal lumen of MgD animals increased significantly, by five times that of the control. The relative supersaturation for calcium oxalate remained constant. Elementary analysis of renal tissue showed an increase in calcium and phosphorus under MgD, in the sense of nephrocalcinosis, but no concretions were detected (no nephrolithiasis). Conclusion In contrast to earlier studies, there is no evidence that hyperoxaluria is responsible for the possible development of urolithiasis in MgD. This was confirmed by calcium phosphate deposits in renal tissue, even though there was no evidence of oxalate urolithiasis. The increase in plasma oxalate seems to be completely compensated by strongly increased oxalate secretion into the intestinal lumen. [ABSTRACT FROM AUTHOR]

Background: Social network methods have improved our understanding of sexually transmitted disease transmission dynamics, and may be of use in routine field operations for partner notification.Goal: To augment traditional syphilis-control activities with social network methods in an Atlanta area with high syphilis morbidity.Study Design: Disease investigators conducted interviews, used network diagrams to prioritize their work, and relied on network connections for finding hard-to-reach persons.Results: A total of 396 contacts were elicited from 48 infected and 50 uninfected persons. The cumulative prevalence of syphilis was 12.6%, and 24 persons infected with HIV were identified. Network methods disclosed a large, interconnected group (276 persons) characterized by high network centrality and the substantial presence of small, interactive subgroups (microstructures).Conclusion: The network approach is a feasible field technique, and can identify core groups involved in the intense transmission of syphilis. The targeted, network-based approach may be useful in attempts to eliminate syphilis. [ABSTRACT FROM AUTHOR]

Background and Objectives: Partner notification has been the cornerstone for the prevention and control of syphilis in the United States. This technique may not make full use of contextual data that an ethnographic and social network approach can offer.Goals Of the Study: The occasion of a syphilis outbreak among young people was used to investigate the applicability of a social network approach and to test the validity of several traditional approaches to syphilis epidemiology.Study Design: An outbreak of syphilis was investigated by interviewing both infected and noninfected people, by directing resources based on network association, by creating and evaluating network diagrams as an aid to the epidemiologic process, and by including ethnographic observations as part of outbreak management.Results: Diagrammatic display of network growth provided a useful alternative to the traditional epidemic curve. Case prevention was demonstrated by identifying uninfected people with multiple concurrent exposures. Concurrent, overlapping exposure in infected people rendered traditional "source" and "spread" criteria moot.Conclusions: The current discussions of partner notification may be informed by recognizing that it is a subset of a broader and potentially more powerful approach. This approach calls some basic tenets of syphilis epidemiology into question. [ABSTRACT FROM AUTHOR]

Objectives: This study evaluated the effectiveness of the Center for Executive Medicine (CEM) concierge primary care practice on preventive colorectal cancer (CRC) screening rates relative to local and national comparator data.Methods: We performed an electronic medical record search encompassing our entire patient population who are between the ages of 50 and 75 years to determine the rate of CRC screening. We compared this rate with the average rate of Medicare Advantage plans reported by our Independent Physician Association (IPA) in 2015 and national health plans reported by the National Committee for Quality Assurance in 2014.Results: The CEM had a CRC screening rate of 90.2%, which was significantly higher than local IPA Medicare Advantage plans (63.3%) and National Committee for Quality Assurance national plans (57.7%-66.5%). CEM members were significantly more likely than were IPA members to undergo screening (odds ratio 1.425, 95% confidence interval 1.348-1.507, P < 0.0001).Conclusions: These results suggest that the CEM practice strategy and processes increase CRC screening rates. [ABSTRACT FROM AUTHOR]

Background: The establishment of long-term uveal melanoma (UM) cell lines is difficult. However, studying living cells and their behaviour in the presence of other cells and the extracellular matrix is important in terms of understanding tumour biology and malignant behaviour. We have established three UM cell lines and report a first characterisation of these cell lines. Methods: Three established UM cell lines (UMT2, UMT26 and UMT33) were analysed according to their morphologic characteristics, melanocytic differentiation, adhesion on different extracellular matrices and proliferative activity. Copy number changes of chromosomes 1, 3, 6 and 8 were studied by multiplex ligation-dependent probe amplification (MLPA). Oncogenic mutations in UM involving exons 4 and 5 of GNAQ and GNA11, respectively, were analysed by sequencing. Results: All cell lines grew in suspension. UMT2 cells were homogeneous, UMT26 and UMT33 cells heterogeneous with regard to cell size and pigmentation. All UM cell lines revealed a melanocytic differentiation. UMT2 and 33 adhered on various extracellular matrices, while UMT26 only adhered to basal membrane extract (BME). This difference corresponded to the different expression of various integrins. Ki67 was expressed by 89 % of UMT2 and 95 % of UMT33 cells, which thus were in a proliferative stage, while only 2 % of UMT26 cells revealed immunostaining for this proliferation marker. The doubling time of UMT2 was 3 days, 12 days for UMT33, and circa 3-4 months for UMT26. MLPA revealed disomy 3 in UMT2 and monosomy 3 in UMT33. The same point mutation was found in UMT2, 26 and 33, in exon 5 of GNA11 at codon 209 (p.Q209L). Conclusions: The establishment of UM cell lines under serum-free conditions is possible. Characterisation of UMT2, 26, and 33 revealed obvious differences in cytomorphology, melanocytic differentiation, adhesion on extracellular matrices, and proliferative activity. UMT2, 26 and 33 showed the same oncogenic mutation in exon 5 of GNA11. [ABSTRACT FROM AUTHOR]

Abstract: The stellarator fusion experiment Wendelstein 7-X (W7-X) is at present in assembly at the Max-Planck Institut für Plasmaphysik (IPP). The toroidal plasma with a ring diameter of 11m and an average plasma diameter of 1.1m is contained within the plasma vessel. Its form is dictated by the shape of the plasma. The form of the plasma is controlled by the coil system configuration. To control the plasma form it is necessary that all the 20 planar and 50 non-planar coils should be positioned within a tolerance of 1.5mm. To meet this requirement a complex coil support structure was created, consisting of the central support ring and the different inter coil supports. The coils and the support structure are enclosed within the outer vessel with its domes and openings. The space between the outer and the plasma vessel is called cryostat because the vacuum inside provides thermal insulation of the magnet system, and the entire magnetic system is then be cooled down to 4K. Due to the different thermal movements the plasma vessel and the central support ring have to be supported separately. The central support ring is held by 10 cryo legs. The plasma vessel supporting system is divided into two separate systems, allowing horizontal and vertical adjustments to centre the plasma vessel during thermal expansion. This paper aims to give an overview of the main components in the cryostat like the plasma vessel, the outer vessel, the ports and the different support systems. It describes the current manufacturing and assembly status and the associated problems of these components, using pictures and text. This paper does not describe the general assembly situation or time schedules of the Wendelstein 7-X. [Copyright &y& Elsevier]

Abstract: One of the most complicated tasks during the assembly of the Wendelstein W7-X is the installation of the superconductive coil system. The entire magnet system is enclosed between the Outer Vessel and the plasma vessel in high vacuum at 4K. The coils are supported by a support structure, the Central Support Structure (CSS). The CSS carries all 70 coils, and it is designed as a closed ring made of 5 modules (10 half modules). The whole structure is supported by 10 Cryolegs which rest on the machine base. This paper describes the final design and manufacture of these Cryolegs. [Copyright &y& Elsevier]

Abstract: The paper presents experimental results on an in situ optical absorption study of reduction/oxidation processes in YAlO3. The increase in the absorption of the bands at 22,000 and 40,000cm–1 during annealing in an oxidizing atmosphere as well as their bleaching during reduction were studied in YAlO3 and YAlO3:Nd crystals in the temperature range 600–1000K. The oxidation and reduction kinetics were analyzed by means of exponential decay modeling as well as in the framework of different models, taking into account diffusion and quasi-chemical reactions of the phototropic centers. [Copyright &y& Elsevier]

Abstract: The elemental composition of 3,4-methylenedioxymethamphetamine (MDMA) powders and tablets was determined. The objective was the identification of the synthesis method and application of the elemental profile in comparative analysis. The developed analytical method comprised the digestion of a sample followed by quantitative analysis with inductive coupled plasma mass spectrometry (ICP-MS) and inductive coupled plasma atomic emission spectroscopy (ICP-AES). The sample collection consisted of a unique set of MDMA powders (57) from illicit production sites and MDMA tablets (97) taken from large seizures (over 500 tablets) in the Netherlands. The production method of MDMA could be determined for 89 of the 97 tablets. In 84 cases reductive amination using Pt as the catalyst was used, in four cases reductive amination using NaBH4 or a similar reducing agent was employed and one mixed sample (Pt and B) was found. None of the MDMA tablets were assigned to the aluminium amalgam method. Using the elemental profile, 13 links were identified within the 97 MDMA tablets using cluster analysis based on Pearson correlations. Of these links 10 were corroborated by additional analyses. [Copyright &y& Elsevier]

Introduction: We investigated the effects of standard oral anticholinergic treatment with tolterodine in children with neurogenic bladder over a 5-year follow-up period and focused on treatment satisfaction, patient compliance and urodynamic parameters. Material and Methods: The follow-up consisted of regular visits and urodynamic evaluation at least once a year. The patients or their parents were interviewed to evaluate voiding behavior, as well as factors leading to lower patient compliance and deterioration in urodynamic parameters. Results: Of the 43 patients evaluated, 30 (70%) took their anticholinergic medication consistently and 13 (30%) sporadically. The mean bladder capacity was 354.7 ml in the first group but only 214.7 ml in the noncompliant group (p < 0.001). The mean maximal detrusor pressure decreased from 42.2 to 33.6 cm H2O in the compliant group (p < 0.001) and from 49.7 to 46.4 cm H2O in the noncompliant group (p = 0.21). The mean detrusor compliance increased from 18.9 to 19.3 ml/cm H2O in the compliant group (p = 0.63) and from 11.8 to 12.3 ml/cm H2O in the noncompliant group (p = 0.87). Side effects such as dry mouth (11/13) and dizziness (7/13) were common in the noncompliant group, whereas only 5/30 reported dry mouth in the compliant group. Conclusions: These data demonstrate the efficacy and tolerability of tolterodine over a long follow-up period. The results are promising in view of the fact that the patients will probably require life-long medication. Nevertheless, anticholinergic side effects still cause some patients to refuse regular medication, which results in a poorer urodynamic outcome. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Hypermethylation of tumor-suppressor genes has been implicated in the pathogenesis of human cancers. This study was designed to examine the methylation profiles of a selected group of p53 target genes (APAF-1, CASP-8, DAPK-1, IGFBP-3) and to correlate the findings with the histopathological characterization of testicular germ cell tumors (TGCT). Promoter methylation status was analysed by highly sensitive real-time methylation-specific PCR in 46 primary TGCTs (26 seminomas and 20 nonseminomas) and 15 normal testicular tissue samples. APAF-1 methylation was detected in all of the seminomatous and nonseminomatous TGCTs as well as in 60% of normal testicular tissue. Methylation of DAPK-1 was frequent in seminomas (50%) and nonseminomas (20%), but not in normal testicular tissue (6%). The degree of DAPK-1 methylation correlated with the clinical stage of the disease (P=0.05) and was useful in differentiating seminomatous from nonseminomatous, and malignant from nonmalignant testicular tissue (P=0.04 and 0.02, respectively). The APAF-1 methylation index achieved a highly significant differentiation between seminomatous or nonseminomatous tissue and nonmalignant testicular tissue (P=0.0001). In testicular tumorigenesis, promoter methylation of specific p53 target genes occurs at early stage but to varying degrees. Methylation also occurs in normal testicular tissue, which is in contrast to findings in other urogenital malignancies. Further studies will be necessary to determine whether the methylation level may be used as marker for risk estimation, especially in clinical stage I disease. [Copyright &y& Elsevier]

To examine the significance of the methylation level of the p53 target and tumour suppressor genes apoptotic protease activating factor-1 (APAF-1) and death-associated protein kinase-1 (DAPK-1) in 80 microdissected tumour samples from transitional cell carcinoma (TCC) of the bladder and 80 tumour samples from clear-cell renal cell carcinoma (RCC) as well as from non-tumourous bladder and kidney tissue. Growth-inhibitory effects of the demethylating agents 5-Aza-2'-deoxycytidine (5-Aza-CdR) and zebularine were investigated in TCC and RCC cell lines. The methylation frequency of APAF-1 (DAPK-1) was 100% (77%) in TCC and 100% (33%) in RCC. The methylation levels of APAF-1 could differentiate between the individual tumour stages in TCC as well as in RCC. The APAF-1 methylation levels in RCC were significantly higher in tumours larger than 4 cm and in high-grade tumours. The methylation frequencies in normal tissue for APAF-1 (DAPK-1) were 11% (8%) in bladder tissue and 9% (5%) in kidney tissue. The growth-inhibitory effect of the demethylating agents in TCC (RT4, T24) and RCC (A498, ClearCa-5) cell lines resulted in a 17-132% prolongation of the doubling time (DT). In RCC cell lines, zebularine was superior to 5-Aza-CdR in achieving a DT prolongation. Quantitative real time RT-PCR detected a re-expression of mRNA transcripts of APAF-1 or DAPK-1. In conclusion, demethylating agents effectively retard growth of TCC and RCC cell lines. Methylation level analysis of specific genes has the potential for further tumour characterisation in TCC and RCC. [ABSTRACT FROM AUTHOR]

Clinical stage I (CS I) seminoma has been the subject of various studies aimed at finding the ideal treatment. Due to its high radiosensitivity, radiotherapy has been the standard approach for decades. However, the fact that CS I seminoma has a recurrence rate of only 15–20% has prompted many suggestions for better treatment stratification offering surveillance therapy for a subgroup of patients. Moreover, carboplatinum-based monochemotherapy has been the topic of various retrospective studies demonstrating equal effectiveness for adjuvant chemotherapy with one cycle of carboplatin. Since seminoma affects men in their mid-30s, only few reports have been published on long-term survival with reference to radiotoxicity and secondary malignancies. Long-term side effects and secondary malignancies pose an increasing problem for long-term survivors of primary malignancies treated by chemo- or radiotherapy. This becomes evident after a follow-up of 15 years. Since recent studies have disclosed unexpectedly high long-term morbidity and mortality after irradiation, this article critically reviews the value of radiotherapy and carboplatinum-based chemotherapy as equally effective treatment options for CS I seminoma. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Despite rapid decompression of the upper urinary tract, some patients show signs of systemic inflammatory response syndrome (SIRS) or septic shock syndrome when infected hydronephrosis is diagnosed. Clinical and biological parameters were analyzed retrospectively in 189 patients diagnosed with hydronephrosis regarding disease severity as well as microbiological and antibiotic features. Fifty of the 189 patients had positive urine culture in the renal pelvis and were included in the study. Fifteen patients had to be placed in the intensive care unit and two patients developed severe septic signs. An initial body temperature above 38.5°C ( P=0.0004) and an elevated BMI ( P=0.002) were the only parameters that indicated a higher risk of developing SIRS or sepsis. Typical biological parameters were not helpful in differentiating patients who will develop urosepsis. Further research is necessary to provide conclusive evidence of the value of other early prognostic markers in patients with infected hydronephrosis. [ABSTRACT FROM AUTHOR]

Locally confined prostate cancer (PCa) can be treated by various treatment options (e.g. radical prostatectomy or radiation therapy) with comparable results but different possible side effects. Therefore, treatment recommendations can vary between urologists and radiation oncologists. In 2001 the Charité-Campus Benjamin Franklin (CBF, Berlin), established the first interdisciplinary consulting service for prostate cancer patients in Germany. The aim was to offer a comprehensive and neutral consultation on all treatment options and to make treatment recommendations. The study examines what benefits may be derived from this type of consultation. A total of 362 patients presented to the consulting service between May 2001 and April 2003. Two questionnaires were used. The first one contained epidemiological questions as well as questions covering information already available on PCa. It also examined feelings and fears about the disease and possible treatment options. The second questionnaire was completed 2 weeks after the consultation to evaluate the treatment decision, determine the patient’s satisfaction with the consultation and trace the development of feelings and fears. Of the patients, 334 (92.2%) were completely assessable. All patients had already obtained information about the disease and possible treatment options and wished to be involved in the decision-making process through objective and neutral consultation. Nearly all of them had a great fear of the possible side effects of therapy. Such a comprehensive consultation is time-consuming (average of 35 min) but largely received a very positive assessment in that a total of 66% found it either helpful (n=74, 22%) or very helpful (n=147, 44%). Patients felt they had been completely informed in 92% of the cases. Only 22 (9.7%) had still failed to make a decision after 2 weeks, 115 patients had stage T1c, PSA<10 ng/ml and a Gleason score =7. In these cases an equivalent recommendation for radical prostatectomy, percutaneous radiotherapy or permanent seed implantation was given. Of these, 49 (43.4%) decided on the surgical intervention, 48 (42.5%) on a type of radiotherapy and only 18 (15.6%) remained undecided. The histological examination of prostatectomy specimens from patients who had decided to undergo radical surgery at CBF showed a significant decrease in the rate of extracapsular disease extension (=T3) from 38% to 20% during the observation period. The interdisciplinary approach has made the process of deciding on an appropriate treatment much easier for the patient. The time-consuming consultation enables better selection of individual treatment modalities and their possible side effects from the point of view of both the patients and the attending physicians. In this study, patients chose either radical surgery or radiotherapy with equal frequency. [ABSTRACT FROM AUTHOR]

Schostak M, Wloch H, Müller M, Schrader M, Offermann G, Miller K. Optimizing open live-donor nephrectomy – long-term donor outcome. Clin Transplant 2004: 18: 301–305. © Blackwell Munksgaard, 2004 The technique of laparoscopic or retroperitoneoscopic donor nephrectomy has been increasingly propagated in recent years. The central advantage is supposed to be a reduction of perioperative discomfort. However, there have not been many reports describing the subjective feeling associated with an open donor nephrectomy, particularly with respect to the pain level in the perioperative and long-term course. This retrospective study examines the perioperative pain and morbidity and long-term outcome of living kidney donors from 35 yr of experience at the University Hospital Benjamin Franklin of the Free University of Berlin. A total of 102 living kidney donors were asked to fill out a questionnaire. Five epidemiological questions were posed and the rest dealt mainly with lasting subjective and objective surgical impairments. There were also questions relating to the perioperative pain level (VAS/NAS-Score). In addition, basic information was obtained regarding the donor's current health status (physical examination, serum creatinine; sometimes also ultrasound, protein IU, blood pressure), and/or examinations were performed. The mean age at the time of donation was 45.5 and 55% were women. Donor nephrectomies were left-sided in 78 cases and right-sided in 24. There was a total complication rate of 53%, but serious complications only occurred in two cases (1.9%). A total of 53 donors could be reached. Although 41.5% felt they had a lasting impairment, somatic sequelae like respiratory, abdominal or scar problems were rare, affecting a maximum of only four patients in each case. Fifteen patients reported neurological problems such as sensory disturbances. The mean serum creatinine was 89.9 μmol/L in female and 114.2 μmol/L in male donors. Microalbuminuria was found in 22.6% of the donors, hypertension in 35.8%. Persistent pain was reported by 20.7%, its occurrence being permanent in two of the donors and very frequent in one. All the others rarely have pain. The median perioperative VAS/NAS score was 8 on the first day after surgery, 5 after 1 wk and 1 after 1 month. The analgesia was rated as good or very good by 71%. Everyday life was managed as well as before surgery after 2–4 wk by the highest percentage (42%) of patients, but working capacity was only regained after 1–3 months by a comparable percentage (44%). Forty-six percent had a very good and 33% a good feeling after the kidney donation. The relationship to the recipient had intensified in most cases. Ninety-one percent would again decide in favor of a donation. Donor nephrectomy in an open technique is a safe and reliable procedure with low morbidity. After a median post-operative period of 7 yr, however, 42% of the donors still report general impairment due to the intervention, although concrete somatic problems were only detected in a few cases. Nearly all these patients underwent surgery in a full flank position. Wound-healing impairments were also significantly more frequent with this surgical technique. This positioning should thus be avoided. The post-operative pain level was relatively high, but a marked improvement was achieved in the course of the observation period by optimizing analgesic management. [ABSTRACT FROM AUTHOR]

: BackgroundStudies on kidney transplantation have thus far mainly dealt with surgical techniques, immunology, and transplant tolerance. Disturbed mineral metabolism after renal denervation has not received much attention. Basic physiological research in short-term experiments has shown that experimental renal denervation in rats leads to parathormone (PTH)-independent hyperphosphaturia (HPU). HPU and other metabolic complications also have been described after clinical kidney transplantation. Furthermore, there is an unexpected increase in the risk of bone fracture. However, these studies have examined an organism pre-damaged with regard to the parathyroid and immunosuppression. Experimental investigations in syngeneic rats were performed to see whether HPU also occurs after transplantation and thus after denervation and which target organs are involved.: MethodsThirty-six male Lewis rats subjected to laparotomy (n = 12), unilateral nephrectomy (n = 12), or unilateral transplantation and bilateral nephrectomy (n = 12) were observed for 18 weeks.: ResultsAnimals that underwent transplantation had a significant loss of phosphate in the urine not associated with decreased calcium, phosphate, or magnesium in bone. Stability test showed no deterioration, despite a slight increase in the bone parameters of alkaline phosphatase, cyclic AMP, and hydroxyproline with unchanged calciotropic hormones. Nephrocalcinosis was not observed. Parallel to HPU, there was a compensatory reduction in fecal phosphate excretion.: ConclusionsThe loss of phosphate after clinical kidney transplantation in the predamaged parathyroid hormone control system as well as immunosuppression and a surprising increase in the incidence of bone fractures may be explained by the denervation-related loss of phosphate. The lack of intestinal counter-regulation could be an important pathomechanism. [Copyright &y& Elsevier]

Summary. We attempted to characterize the cells collected from the rete testis via ultrasonographically guided puncture. Unilateral puncture of the rete testis was performed in nine men with obstructive azoospermia and 51 men with nonobstructive azoospermia. All the aspirated samples from the rete testis were observed via confocal scanning laser microscope and some of them after fluorescent in situ hybridization techniques. Then therapeutic testicular biopsy was performed in the punctured testis of each man. Spermatozoa were found in all rete testis samples and all biopsy samples from obstructed men. Twenty-two nonobstructed men demonstrated absence of spermatozoa in biopsy samples. Twenty-nine nonobstructed men showed spermatozoa in biopsy material and 24 of these men (82%) had demonstrated spermatozoa in rete testis samples. There were no significant differences in fertilization and cleavage rate between intracytoplasmic sperm injection trials using biopsy spermatozoa and rete testis spermatozoa both in obstructed and nonobstructed men. Considering that puncture of the rete testis does not reduce the volume of testicular parenchyma, is less invasive and apparently causes less detrimental effect on testicular vasculature than biopsy, puncture of rete testis is recommended as first line approach for the treatment of azoospermic men. If puncture is negative for spermatozoa in nonobstructed men, biopsy is indicated. [ABSTRACT FROM AUTHOR]

• It is shown that the M1 design based on the use of a thin single-crystal rhodium (ScRh) plate and a special WCu composite is feasible and robust. A rhodium nanocrystalline coating (NcRh) is kept as an optional solution. • The mirror is equipped with an adjustment of 3 DOFs (two rotations and translation) keeping a possibility to recover the initial mirror position without an additional readjustment. • A compatibility with in-situ repetitive cleaning is provided with implementation of the required insulation and gaps. Design option of the RF feeding line connector is presented. • Successful connection between ScRh/WCu samples is achieved. The high quality of the diffusion bonding is confirmed with FIB and metallography examinations, and by mechanical test resulting in the average shear strength of 233.3 MPa. The ITER core charge exchange recombination spectroscopy, which contains five in-port optical mirrors, is intended to transfer the visible light emitted by interaction of the plasma with the diagnostic neutral beam to the corresponding spectrometers. The first mirror (M1) is a key and the most vulnerable component of the diagnostics. In order to provide the required mirror lifetime, maintainability and structural integrity, M1 is composed of special materials, i.e. it is made of a thin 1 mm single-crystal rhodium (ScRh) plate diffusion bonded to a specially matched tungsten-copper substrate. A rhodium nanocrystalline coating (NcRh) can be an option. The paper presents the evolution of the M1 design developed for the optical layout of 2018. M1 is adjustable and cleanable with about 100÷500 procedures of 60 MHz plasma discharge. The mirror design is supported by multifield thermal, electromagnetic and structural analyses and uses experimental data of R&Ds made by Forschungszentrum Juelich, Germany. The study confirms the working capacity of the developed mirror solution. [ABSTRACT FROM AUTHOR]